Prognostic value of scalp EEG ictal patterns in epilepsy surgery of hippocampal sclerosis.

BACKGROUND: Temporal lobe epilepsy associated with hippocampal sclerosis (TLE-HS) is a surgically treatable epileptic syndrome. While the core of pre-surgical evaluations rely on video-EEG, recent studies question the necessity of recorded seizures denying a possible role of ictal EEG in surgical decision. This study aims to retrospectively assess the prognostic value of EEG ictal patterns in TLE-HS, in order to identify which patients need further investigations before offering surgery. METHODS: We included TLE-HS patients who underwent surgery with at least one captured seizure during non-invasive pre-surgical video-EEG recordings. They were classified in "mesial" and "lateral/mixed", according to the ictal EEG patterns, defined by the frequency of the discharge (mesial ≥ 5 Hz, lateral < 5 Hz). Seizure outcome was assessed by Engel's Class. Statistical analyses were performed to evaluate associations between EEG patterns and post-surgical outcomes. RESULTS: Sixty-nine exhibited a mesial pattern, forty- two displayed lateral/mixed patterns. Mesial pattern group had a significantly higher rate of postsurgical seizure freedom (82.7% vs. 28.6%). Gender, age of onset, age at surgery, duration of epilepsy, seizure frequency, and lateralization did not influence the outcome. Mesial pattern significantly correlated with favorable outcomes (p < 0.001), suggesting its potential predictive value. CONCLUSION: This retrospective study proposes ictal EEG patterns as possible predictors of postoperative prognosis in TLE-HS. A mesial pattern correlates with better outcomes, indicating a potentially more circumscribed epileptogenic zone. Patients with lateral/mixed patterns may benefit from additional investigations to delineate the epileptogenic zone. Further studies are warranted to validate and extend these findings.

Adjunctive Brivaracetam in Older Patients with Focal Seizures: Evidence from the BRIVAracetam add­on First Italian netwoRk Study (BRIVAFIRST).

BACKGROUND: The management of epilepsy in older adults has become part of daily practice because of an aging population. Older patients with epilepsy represent a distinct and more vulnerable clinical group as compared with younger patients, and they are generally under-represented in randomized placebo-controlled trials. Real-world studies can therefore be a useful complement to characterize the drug's profile. Brivaracetam is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A and approved as adjunctive therapy for focal seizures in adults with epilepsy. OBJECTIVE: The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive brivaracetam in older patients (≥65 years of age) with epilepsy treated in a real-world setting. METHODS: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a 12-month retrospective multicenter study including adult patients prescribed adjunctive brivaracetam. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events and the incidence of adverse events. Data were compared for patients aged ≥65 years of age ('older') vs those aged <65 years ('younger'). RESULTS: There were 1029 patients with focal epilepsy included in the study, of whom 111 (10.8%) were aged ≥65 years. The median daily dose of brivaracetam at 3 months was 100 [interquartile range, 100-175] mg in the older group and 100 [100-200] mg in the younger group (p = 0.036); it was 150 [100-200] mg in both groups either at 6 months (p = 0.095) or 12 months (p = 0.140). At 12 months, 49 (44.1%) older and 334 (36.4%) younger patients had a reduction in their baseline seizure frequency by at least 50% (p = 0.110), and the seizure freedom rates were 35/111 (31.5%) and 134/918 (14.6%) in older and younger groups, respectively (p < 0.001). During the 1-year study period, 20 (18.0%) patients in the older group and 245 (26.7%) patients in the younger group discontinued brivaracetam (p = 0.048). Treatment withdrawal because of insufficient efficacy was less common in older than younger patients [older: n = 7 (6.3%), younger: n = 152 (16.6%); p = 0.005]. Adverse events were reported by 24.2% of older patients and 30.8% of younger patients (p = 0.185); the most common adverse events were somnolence, nervousness and/or agitation, vertigo, and fatigue in both study groups. CONCLUSIONS: Adjunctive brivaracetam was efficacious, had good tolerability, and no new or unexpected safety signals emerged when used to treat older patients with uncontrolled focal seizures in clinical practice. Adjunctive brivaracetam can be a suitable therapeutic option in this special population.

Adjunctive Brivaracetam in Focal Epilepsy: Real-World Evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST).

BACKGROUND: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. OBJECTIVE: This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice. METHODS: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure-freedom, seizure response (≥ 50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed. RESULTS: A total of 1029 patients with a median age of 45 years (33-56) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs (p < 0.001); the corresponding values for ≥ 50% seizure frequency reduction were 47.9%, 29.7%, and 42.8% (p < 0.001). There were no statistically significant differences in seizure freedom and seizure response rates by use of strong EiASMs. The rates of seizure freedom (20.0% vs. 16.6%;  p = 0.341) and seizure response (39.7% vs. 26.9%; p = 0.006) were higher in patients receiving SCBs than those not receiving SCBs; 265 (25.8%) patients discontinued BRV. AEs were reported by 30.1% of patients, and were less common in patients treated with BRV and concomitant SCBs than those not treated with SCBs (28.9% vs. 39.8%; p = 0.017). CONCLUSION: The BRIVAFIRST provided real-world evidence on the effectiveness of BRV in patients with focal epilepsy irrespective of LEV history and concomitant ASMs, and suggested favourable therapeutic combinations.

Bilateral epileptogenesis in temporal lobe epilepsy due to unilateral hippocampal sclerosis: A case series.

INTRODUCTION: Bitemporal epilepsy (biTLE), a potential cause of failure in TLE surgery, is rarely associated with unilateral HS and could be suggested by not lateralizing ictal scalp EEG/interictal PET-FDG findings. We evaluated the proportion of biTLE in a population of drug-resistant TLE-HS subjects who underwent intracranial investigation for lateralizing purpose. METHODS: We retrospectively included all consecutive refractory TLE-HS patients and not lateralizing ictal scalp EEG/interictal PET-FDG findings, investigated by intracranial bilateral longitudinal hippocampal electrodes. Demographic characteristics, electroclinical findings and seizure outcome were evaluated. RESULTS: We identified 14 subjects (7 males; mean age 39.5 years; mean age at disease onset 14.4 years), 7 of them had biTLE diagnosed after intracranial investigations. In the remaining 7 with unilateral epileptogenesis (uniTLE) anterior temporal lobectomy was performed (6/7 were in Engel class I). Preoperative neuropsychological assessment differentiated biTLE from uniTLE, as it was normal in six uniTLE patients but only in one with biTLE (p < 0.05). CONCLUSIONS: Not lateralizing ictal scalp EEG and functional imaging findings in TLEHS should alert about the possibility of a true biTLE also in presence of unilateral findings at MRI. Intracranial investigations with bilateral longitudinal hippocampal electrodes can localize the EZ with a good risk-benefit profile. Consistently with the warning on memory functions in TLE patients explored by using longitudinal hippocampal electrodes, further studies are needed to better define the optimal investigation strategy.

Lacosamide as first add-on or conversion monotherapy: A retrospective real-life study.

PURPOSE: Lacosamide (LCM), the R-enantiomer of 2-acetamido-N-benzyl-3-methoxypropionamide, is a newer approved antiseizure medication characterized by a novel pharmacodynamic and favorable pharmacokinetic profile that was approved as adjunctive treatment for adults with focal onset and focal to bilateral tonic-clonic seizures in 2008, and recently also for monotherapy. The aim of this study was to evaluate the effectiveness and tolerability of LCM as first add-on or conversion monotherapy in adult subjects with focal epilepsy. METHODS: We retrospectively included all adult patients who received LCM as first add-on regimen or as substitution monotherapy at least 12 months before starting the chart review, with a historical baseline of 6 months prior to day of the first administration of LCM. The choice of treatment was made independently by the epilepstologists, according to routine clinical practice. Clinical data were obtained at 3, 6, and 12 months after subjects started LCM and then analyzed to assess retention rate, seizure freedom, and adverse events (AE). RESULTS: A total of 101 patients (58 men) with a mean age of 44 years and a median epilepsy duration of 6.6 years (range 1-53) were included in the study. At 12 months 72 patients retained LCM, 54 (75%) of them were seizure free, 44 (81.5%) in monotherapy and 10 (18.5%) in add-on LCM treatment. Among all subjects, 31 (57.4%) were free from seizure under LCM monotherapy throughout the entire observation period. Thirty one out of 72 (43%) PwE who retained LCM at 12 months, were free from seizures throughout the entire observation period. The maintenance median dosage of LCM was 200 mg/day. Ten (10%) subjects reported mild to moderate AE, most commonly drowsiness and dizziness. No serious AE were documented. CONCLUSIONS: This real-life study confirms that LCM is an effective and well tolerated treatment option as first add-on or conversion monotherapy for focal seizures.

Seizures induced by micturition: A rare form of reflex epilepsy.

•Micturition-induced seizures are a rare form of reflex epilepsy.•Video-EEG monitoring is crucial for diagnosis.•Symptomatogenic zone involves mesial fronto-parietal cortex.

Long-term safety, efficacy, and quality of life during adjunctive brivaracetam treatment in patients with uncontrolled epilepsy: An open-label follow-up trial.

OBJECTIVES: The primary objective of this long-term follow-up (LTFU) trial was to evaluate the long-term safety and tolerability of brivaracetam (BRV). The secondary objective was to evaluate the maintenance of efficacy of BRV (including quality of life) over time. METHODS: This open-label, multicenter, flexible-dose trial (N01379 [NCT01339559]) was conducted in adults (≥16 years) with focal or generalized-onset seizures, who had participated in a placebo (PBO)-controlled trial of adjunctive BRV (N01258: NCT01405508 or N01358: NCT01261325). RESULTS: Seven hundred and sixty-six patients received BRV in this LTFU trial (753 had focal seizures and 13 had generalized-onset seizures). Kaplan-Meier-estimated retention was 71.9% at 12 months, and 53.7% at 36 months. Treatment-emergent adverse events (TEAEs) were reported by 643 (83.9%) patients, most commonly headache (104 [13.6%] patients) and dizziness (100 [13.1%] patients). Two hundred and fifty-seven (33.6%) patients had drug-related TEAEs, most commonly somnolence (49 [6.4%] patients) and dizziness (41 [5.4%] patients). Permanent discontinuation of BRV due to TEAEs occurred in 91 (11.9%) patients. Patients with focal seizures had a median percentage reduction in focal seizure frequency of 52.0% and 51.7% were 50% responders (sustained over time); 26.0% were seizurefree for 6 months, and 17.9% were seizurefree for 12 months. 42.4% of patients at 12 months and 46.8% at 24 months had clinically meaningful improvements in Patient Weighted Quality of Life in Epilepsy Questionnaire 31 total score. CONCLUSIONS: In this select group of patients who entered the LTFU trial, BRV was generally safe and well tolerated. Results indicate the long-term efficacy of BRV in patients with focal seizures.

Temporal lobe epilepsy surgery in children and adults: A multicenter study.

OBJECTIVE: To assess seizure and cognitive outcomes and their predictors in children (<16 years at surgery) and adults undergoing temporal lobe epilepsy (TLE) surgery in eight Italian centers. METHODS: This is a retrospective multicenter study. We performed a descriptive analysis and subsequently carried out multivariable mixed-effect models corrected for multiple comparisons. RESULTS: We analyzed data from 511 patients (114 children) and observed significant differences in several clinical features between adults and children. The possibility of achieving Engel class IA outcome and discontinuing antiepileptic drugs (AEDs) at last follow-up (FU) was significantly higher in children (P = .006 and < .0001). However, percentages of children and adults in Engel class I at last FU (mean ± SD, 45.9 ± 17 months in children; 45.9 ± 20.6 months in adults) did not differ significantly. We identified different predictors of seizure outcome in children vs adults and at short- vs long-term FU. The only variables consistently associated with class I outcome over time were postoperative electroencephalography (EEG) in adults (abnormal, improved,odds ratio [OR] = 0.414, P = .023, Q = 0.046 vs normal, at 2-year FU and abnormal, improved, OR = 0.301, P = .001, Q = 0.002 vs normal, at last FU) and the completeness of resection of temporal magnetic resonance (MR) abnormalities other than hippocampal sclerosis in children (OR = 7.93, P = .001, Q = 0.003, at 2-year FU and OR = 45.03, P < .0001, Q < 0.0001, at last FU). Cognitive outcome was best predicted by preoperative performances in either age group. SIGNIFICANCE: Clinical differences between adult and pediatric patients undergoing TLE surgery are reflected in differences in long-term outcomes and predictors of failures. Children are more likely to achieve sustained seizure freedom and withdraw AEDs after TLE surgery. Earlier referral should be encouraged as it can improve surgical outcome.

Ictal Asystole in Drug-Resistant Focal Epilepsy: Two Decades of Experience from an Epilepsy Monitoring Unit.

BACKGROUND: Ictal asystole (IA) is a rare event observed in people with epilepsy (PwE). Clinical and IA video-electroencephalographic findings may be helpful in screening for high-risk subjects. Methods: From all PwE undergoing video-EEG for presurgical evaluation between 2000 and 2019, we retrospectively selected those with at least one IA (R-R interval of ≥3 s during a seizure). Results: IA was detected in eight out of 1088 (0.73%) subjects (mean age: 30 years; mean epilepsy duration: 9.6 years). Four out of them had a history of atonic falls. No patients had cardiac risk factors or cardiovascular diseases. Seizure onset was temporal (n = 5), temporo-parietal (n = 1) or frontal (n = 2), left-sided and right-sided in five and two patients, respectively. In one case a bilateral temporal independent seizure onset was recorded. IA was recorded in 11 out of 18 seizures. Mean IA duration was 13 s while mean IA latency from seizure onset was 26.7 s. Symptoms related to IA were observed in all seizures. Conclusion: IA is a rare and self-limiting event often observed during video-EG in patients with a history of atonic loss of consciousness and/or tardive falls in the course of a typical seizure.

Long-term seizure outcome in frontal lobe epilepsy surgery.

PURPOSE: The purpose of this study was to report long-term seizure outcome in patients who underwent frontal lobe epilepsy (FLE) surgery. METHOD: This retrospective study included 44 consecutive subjects who underwent resective surgery for intractable FLE at IRCCS NEUROMED (period 2001-2014), followed up for at least 2 years (mean: 8.7 years). All patients underwent noninvasive presurgical evaluation and/or invasive electroencephalography (EEG) monitoring when nonconcordant data were obtained or epileptogenic zone was hypothesized to be close to the eloquent cortex. Electroclinical, neuroimaging, surgical data, and histology were compared to seizure outcome. RESULTS: Mean epilepsy duration was 19 years; mean age at surgery was 31.6 years. Preoperative magnetic resonance imaging (MRI) showed a frontal lesion in 86.4 % of cases. Scalp video-electroencephalography (VEEG) monitoring detected a focal ictal onset in 90% of cases. Twenty-seven patients (61.4%) underwent invasive recordings. Resections involved dorsolateral (47.7%), medial (9%), orbital (13.6%), and rolandic (13.6%) region. Lobectomy within functional boundaries was performed in the remaining 7 cases (16%). Transient and permanent neurological deficits were observed in 2 and 3 cases, respectively. Histology revealed focal cortical dysplasia (45.5%), World Health Organization (WHO) I-II grade tumors (15.9%), gliosis (22.7%), vascular malformations (4.5%), Rasmussen encephalitis (6.8%), and normal tissue (4.5%). At last observation 68.1% of patients were in Engel's class I, 11.4% in class II, 9% in class III, and 11.4% in class IV. A favorable outcome was associated with focal ictal scalp EEG onset (p = 0.0357). CONCLUSION: Surgery is a safe treatment option in drug-resistant FLE with a satisfying long-term outcome. These data highlight the importance of an appropriate selection of potential surgical candidates.

Possible autoantibody-negative limbic encephalitis after anterior temporal lobectomy for hippocampal sclerosis.

PURPOSE: Amnestic syndromes are acknowledged to be associated to bilateral hippocampal damage. MATERIALS AND METHODS: We briefly report the case of a young man who underwent anterior left temporal lobectomy for a medically refractory temporal lobe epilepsy due to hippocampal sclerosis with an excellent seizure and neuropsychological outcome. Approximately 10 years later, he presented with a subacute severe global amnesia and neuroimaging findings of a damage involving the contralateral mesial temporal lobe structures. RESULTS: A diagnosis of a possible autoimmune encephalitis was made. CONCLUSIONS: Due to its peculiarities (compared with other cases of bilateral temporal lesions, the damage occurred on two distinct occasions), this case might contribute to shed light on the issue of the possible contralateral reorganization of memory processes subserved by the mesial temporal lobe structures chronically involved in epileptogenesis.

Epilepsy surgery of "low grade epilepsy associated neuroepithelial tumors": A retrospective nationwide Italian study.

OBJECTIVE: To analyze the attitude and results of Italian epilepsy surgery centers in the surgical management of "low grade epilepsy associated neuroepithelial tumors" (LEATs). METHODS: We conducted a retrospective study enrolling 339 consecutive patients with LEATs who underwent surgery between January 2009 and June 2015 at eight Italian epilepsy surgery centers. We compared demographic, clinical, pathologic, and surgical features of patients with favorable (Engel class I) and unfavorable (Engel class II, III, and IV) seizure outcome. In addition, we compared patients with tumor-associated focal cortical dysplasia (FCD) and patients with solitary tumors to identify factors correlated with FCD diagnosis. RESULTS: Fifty-five (98.2%) of 56 patients with medically controlled epilepsy were seizure-free after surgery, compared to 249 (88.0%) of 283 patients with refractory epilepsy. At multivariate analysis, three variables independently predict unfavorable seizure outcome in the drug-resistant group. Age at surgery is largely the most significant (p = 0.001), with an odds ratio (OR) of 1.04. This means that the probability of seizure recurrence grows by 4% for every waited year. The resection site is also significant (p = 0.039), with a relative risk (RR) of 1.99 for extratemporal tumors. Finally, the completeness of tumor resection has a trend toward significance (p = 0.092), with an RR of 1.82 for incomplete resection. Among pediatric patients, a longer duration of epilepsy was significantly associated with preoperative neuropsychological deficits (p < 0.001). A statistically significant association was observed between FCD diagnosis and the following variables: tailored surgery (p < 0.001), temporal resection (p = 0.001), and surgical center (p = 0.012). SIGNIFICANCE: Our nationwide LEATs study gives important insights on factors predicting seizure outcome in refractory epilepsy and determining variability in FCD detection. Timely surgery, regardless of pharmacoresistance and oriented to optimize epileptologic, neuropsychological, and oncologic outcomes should be warranted.

Severe and rapidly-progressive Lafora disease associated with NHLRC1 mutation: a case report.

Lafora disease (LD), also known as progressive myoclonic epilepsy-2 (EPM2), is a rare, fatal autosomal recessive disorder typically starting during adolescence in otherwise neurologically normal individuals. It is clinically characterized by insidious of progressive neurological features including seizures, action myoclonus, visual hallucination, ataxia and dementia. Mutations in the laforin (EPM2A) gene on chromosome 6q24 or in the malin gene (NHLRC1) on chromosome 6p22 are responsible of LD phenotype. Diagnostic workup includes genetic analysis as well as axillary skin biopsy with evidence of typical periodic acid-Schiff (PAS)-positive polyglucosan inclusion bodies (Lafora bodies) in the apocrine glands and/or in the eccrine duct. Usually, genotype-phenotype correlations do not reveal substantial differences between patients carrying EPM2A and NHLRC1 mutations, but a few specific NHLRC1 mutations appear to correlate with a late onset and slow progressing LD. We report a case of LD due to compound heterozygote NHLRC1 mutation in an adolescent presenting with severe and atypical electro-clinical features, mimicking an autoimmune encephalopathy, and a rapidly progressive clinical course.

Temporal pole abnormalities detected by 3 T MRI in temporal lobe epilepsy due to hippocampal sclerosis: No influence on seizure outcome after surgery.

PURPOSE: To assess the clinical significance of temporal pole abnormalities (temporopolar blurring, TB, and temporopolar atrophy, TA) detected by using 3 Tesla MRI in the preoperative workup in patients with temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS) who underwent surgery. METHODS: We studied 78 consecutive patients with TLE-HS who underwent surgery and were followed up for at least 2 years. Based on findings of pre-surgical 3 Tesla MRI, patients were subdivided in subgroups according to the presence of TB or TA. Subgroups were compared on demographic, clinical, neuropsychological data and seizure outcome. RESULTS: TB was found in 39 (50%) patients, while TA was found in 32 (41%) patients, always ipsilateral to HS, with a considerable degree of overlap (69%) between TB and TA (p=0.01). Patients with temporopolar abnormalities did not significantly differ from those without TB or TA with regard to sex, age, age of epilepsy onset, duration of epilepsy, history of febrile convulsions or birth complications, side of surgery, seizure frequency at surgery, presence of GTCSs, and, in particular, seizure outcome. On the other hand, TB patients show a less frequent family history of epilepsy (p<.05) while age at epilepsy onset showed a trend to be lower in the TB group (p=.09). Patients with temporopolar atrophy did not significantly differ from those without TA on any variable, except for age at epilepsy onset, which was significantly lower for the TA group (p<.05). History of birth complications and longer duration of epilepsy also showed a trend to be associated with TA (p=.08). Multivariate analysis corroborated the association between temporopolar abnormalities and absence of family history of epilepsy and history of birth complications. CONCLUSIONS: High-field 3 T MRI in the preoperative workup for epilepsy surgery confirms that temporopolar abnormalities are frequent findings in TLE-HS patients and may be helpful to lateralize the epileptogenic zone. Their presence did not influence seizure outcome.

Efficacy and safety of brivaracetam for partial-onset seizures in 3 pooled clinical studies.

OBJECTIVE: To assess the efficacy, safety, and tolerability of adjunctive brivaracetam (BRV), a selective, high-affinity ligand for SV2A, for treatment of partial-onset (focal) seizures (POS) in adults. METHODS: Data were pooled from patients (aged 16-80 years) with POS uncontrolled by 1 to 2 antiepileptic drugs receiving BRV 50, 100, or 200 mg/d or placebo, without titration, in 3 phase III studies of BRV (NCT00490035, NCT00464269, and NCT01261325, ClinicalTrials.gov, funded by UCB Pharma). The studies had an 8-week baseline and a 12-week treatment period. Patients receiving concomitant levetiracetam were excluded from the efficacy pool. RESULTS: In the efficacy population (n = 1,160), reduction over placebo (95% confidence interval) in baseline-adjusted POS frequency/28 days was 19.5% (8.0%-29.6%) for 50 mg/d (p = 0.0015), 24.4% (16.8%-31.2%) for 100 mg/d (p < 0.00001), and 24.0% (15.3%-31.8%) for 200 mg/d (p < 0.00001). The ≥50% responder rate was 34.2% (50 mg/d, p = 0.0015), 39.5% (100 mg/d, p < 0.00001), and 37.8% (200 mg/d, p = 0.00003) vs 20.3% for placebo (p < 0.01). Across the safety population groups (n = 1,262), 90.0% to 93.9% completed the studies. Treatment-emergent adverse events (TEAEs) were reported by 68.0% BRV overall (n = 803) and 62.1% placebo (n = 459). Serious TEAEs were reported by 3.0% (BRV) and 2.8% (placebo); 3 patients receiving BRV and one patient receiving placebo died. TEAEs in ≥5% patients taking BRV (vs placebo) were somnolence (15.2% vs 8.5%), dizziness (11.2% vs 7.2%), headache (9.6% vs 10.2%), and fatigue (8.7% vs 3.7%). CONCLUSIONS: Adjunctive BRV was effective and generally well tolerated in adults with POS. CLASSIFICATION OF EVIDENCE: This analysis provides Class I evidence that adjunctive BRV is effective in reducing POS frequency in adults with epilepsy and uncontrolled seizures.

Temporal pole abnormalities in temporal lobe epilepsy with hippocampal sclerosis: Clinical significance and seizure outcome after surgery.

PURPOSE: To assess the clinical significance of temporal pole abnormalities (temporopolar blurring, TB, and temporopolar atrophy, TA) in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) with a long post-surgical follow-up. METHODS: We studied 60 consecutive patients with TLE-HS and 1.5 preoperative MRI scans who underwent surgery and were followed up for at least 5 years (mean follow-up 7.3 years). Based on findings of pre-surgical MRI, patients were classified according to the presence of TB or TA. Groups were compared on demographic, clinical, neuropsychological data, and seizure outcome. RESULTS: TB was found in 37 (62%) patients, while TA was found in 35 (58%) patients, always ipsilateral to HS, with a high degree of overlap (83%) between TB and TA (p<0.001). Patients with TB did not differ from those without TB with regard to history of febrile convulsions, GTCSs, age of epilepsy onset, side of surgery, seizure frequency, seizure outcome, and neuropsychological outcome. On the other hand, they were significantly older, had a longer duration of epilepsy, and displayed lower preoperative scores on several neuropsychological tests. Similar findings were observed for TA. Multivariate analysis corroborated the association between temporopolar abnormalities and age at onset, age at surgery (for TB only), and lower preoperative scores on some neuropsychological tests. CONCLUSIONS: Temporopolar abnormalities are frequent in patients with TLE-HS. Our data support the hypothesis that TB and TA are caused by seizure-related damages. These abnormalities did not influence seizure outcome, even after a long-term post-surgical follow-up.

Epilepsy surgery in adult-onset Rasmussen's encephalitis: case series and review of the literature.

Rasmussen's encephalitis (RE) is a rare immune-mediated condition characterized by drug-resistant focal epilepsy, progressive neurological, and cognitive deficits associated to unilateral hemispheric atrophy. The onset is typically reported in childhood, although adult cases (A-RE) have been described. While surgical strategies in childhood RE are well defined, little is known about usefulness of epilepsy surgery in A-RE patients. We describe clinical features, surgical approach, and outcome of five A-RE patients who underwent epilepsy surgery, and we review the literature with regard to surgical A-RE cases. We retrospectively studied five A-RE patients aged 21-38 years (mean age 22.8 years) who were followed after surgery for a period ranging from to 1 to 6 years. Demographic, electroclinical, and neuroimaging data were systematically reviewed. Four out of five subjects underwent invasive EEG monitoring to define epileptogenic zone. Epilepsy outcome was defined according to Engel's classification. Surgery consisted of frontal corticectomy in three patients, temporal lobectomy in one, combined temporal lobectomy plus insular, and frontobasal corticectomy in the remaining case. No permanent neurological deficits were observed after surgery. At the last follow-up observation, one patient was seizure-free, two subjects experienced rare disabling seizures, another had moderate seizure reduction, and one had no clinical improvement. Our experience, although limited to few cases, suggests that resective surgery in A-RE may play a role in the context of multidisciplinary therapeutical approach of this severe condition. Since the lack of specific data about surgical options, this topic seems to deserve further investigations and more targeted studies.

Acute postoperative seizures and long-term seizure outcome after surgery for hippocampal sclerosis.

PURPOSE: To assess the incidence and the prognostic value of acute postoperative seizures (APOS) in patients surgically treated for drug-resistant temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS). METHODS: We studied 139 consecutive patients with TLE-HS who underwent epilepsy surgery and were followed up for at least 5 years (mean duration of follow-up 9.1 years, range 5-15). Medical charts were reviewed to identify APOS, defined as ictal events with the exception of auras occurring within the first 7 days after surgery. Seizure outcome was determined at annual intervals. Patients who were in Engel Class Ia at the last contact were classified as having a favorable outcome. RESULTS: Seizure outcome was favorable in 99 patients (71%). Six patients (4%) experienced APOS and in all cases their clinical manifestations were similar to the habitual preoperative seizures. All patients with APOS had unfavorable long-term outcome, as compared with 35 (26%) of 133 in whom APOS did not occur (p<0.001). CONCLUSIONS: Our study suggests that APOS, despite being relatively uncommon in patients undergoing resective surgery for TLE-HS, are associated with a worse long-term seizure outcome. Given some study limitations, our findings should be regarded as preliminary and need confirmation from future larger, prospective, multicenter studies.